AB0362 NEUTROPHIL COUNT REDUCTION 1 MONTH AFTER INITIATING SARILUMAB AND BASELINE SERUM SOLUBLE gp130 LEVELS CAN INDEPENDENTLY PREDICT CLINICAL REMISSION WITHIN 3 MONTH IN RHEUMATOID ARTHRITIS PATIENTS
Authors: T. Yoshikawa, K. Azuma, T. Furukawa, T. Hashimoto, M. Morimoto, N. Azuma, K. Matsui
Journal: Annals of the Rheumatic Diseases (2022)

Background IL-6 contributes significantly to the chronic inflammatory process of rheumatoid arthritis (RA) and is elevated in serum and synovial fluid of RA patients. Sarilumab (SRL), a human anti-human IL-6 receptor alpha monoclonal antibody that blocks the signaling originated by the IL-6/IL-6R complex like tocilizumab (TCZ),is an effective treatment. Recently, an association between the therapeutic effect of TCZ and neutropenia after TCZ initiation was reported[1]. Neutropenia is a common adverse event of SRL in patients with RA, but the relationship between reduced neutrophil count and clinical response to SRL is still inconclusive. In EULAR 2020, we reported the association between serum soluble gp130 levels before SRL treatment and the efficacy of SRL[2]. It is also unclear whether there is a relationship between IL-6 axis cytokines and SRL-induced neutropenia. Objectives The purpose of this study was to determine whether neutropenia at 1 month by SRL predicts clinical remission within 3 months and whether there is an association between IL-6 axis cytokines levels and SRL-induced neutropenia. Methods This research is a retrospective study. We reviewed medical records of RA patients initiating SRL between February 2018 and August 2021 in our hospital. The Clinical Disease Activity Index (CDAI) was evaluated at baseline (before initiating SRL) and 3 months after administration. Clinical remission was defined when CDAI decreased ≤ 2.8. Of the 66 patients treated with SRL, 42 patients with 3 months follow-up, valid CDAI and serum available were enrolled. The ratio of neutrophil counts 1 month after initiating SRL to those at baseline (neutrophil ratio) was also calculated. Serum samples were tested for IL-6 (Human IL-6 Quantikine ELISA Kit, R&amp;D systems), sIL-6R (Human soluble IL-6R alpha Quantikine ELISA Kit, R&amp;D systems) and sgp130 (Human soluble gp130 Quantikine ELISA Kit, R&amp;D systems) using specific ELISAs according to the manufacturer’s instructions. The statistical analyses were performed with EZR 1.55, and p values less than 0.05 were considered significant. Results The median age of patients was 69.0 (IQR: 59.3 - 73.8) years and the median of disease duration was 9.0 (3.0 - 16.0) years. Eighteen (42.9%) patients were biologics and Jakinibs naive. The baseline CDAI was median 16.7 (11.5 - 25.8). When comparing CDAI-remission group (clinical remission: CR) and non-CR group, Patients in the CR group had significantly shorter disease duration, were more Biologic and JAKinib naive, and had greater neutropenia 1 month after starting SRL (0.71 vs 0.94, P=0.0252). There was no significant difference in the baseline serum levels of IL-6, sIL-6R between the CR and non-CR groups, but baseline serum sgp130 levels in the CR group tended to be higher than in the non-CR group (264.9 vs 234.2 ng/mL, P=0.0592). Univariate logistic regression analysis suggested Biologics and JAKinibs naive (odds ratio (OR) 6.68, p = 0.0317), baseline serum sgp130 levels (OR 8.608, P=0.0312) as predictors of CDAI remission treated with SRL at 3 months. Although not significant, neutrophil ratio ≤ 0.8 was associated with achieving remission (OR 6.67, P=0.0537). Univariate logistic regression for neutrophil ratio ≤ 0.8 did not show any relevant factors, including higher baseline serum sgp130 levels (OR 1.25, P=0.782). Conclusion A 20% or greater decrease in neutrophil count after 1 month of SRL treatment and a high baseline serum sgp130 level independently predict clinical remission within 3 months. References [1]Nakajima T, Watanabe R, Hashimoto M, Murata K, Murakami K, Tanaka M, et al. Neutrophil count reduction 1 month after initiating tocilizumab can predict clinical remission within 1 year in rheumatoid arthritis patients. Rheumatol Int. 2021;1rin [2]Yoshikawa T, Furukawa T, Tamura M, Hashimoto T, Morimoto M, Azuma N, et al. FRI0113 THE BASELINE SOLUBLE GP130 IS ASSOCIATED WITH THE RESPONSE OF RHEUMATOID ARTHRITIS PATIENTS TO SARILUMAB. Ann Rheum Dis. 2020;79(Suppl 1):637.1-637. Disclosure of Interests None declared